Aixial Group: Experts in Radiopharmaceutical Development

Understanding the multidisciplinary approach in radiotherapy

Developing radiopharmaceuticals is a multidisciplinary endeavor involving nuclear medicine, radiology, pathology, oncology, dosimetry, and radionuclide imaging, amongst others. In addition to this group of practitioners, clinical trials may also involve a dynamic team comprised of a clinician, nurse, physicist, radiopharmacist, radiographer and administrative staff working together in a detailed choreography depicted below:

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Disciplines involved in radiopharmaceuticals clinical trials:

Close coordination among site interdisciplinary team.

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Orchestrating this choreography requiresstrong relationships and open communication between medical monitors, investigators, radiopharmacists, physicists, Nuclear Medicine Physicians, and other site departmental representatives.  In view of the multi-disciplined resources involved, Aixial’s global team embrace a collaborative approach with all stakeholders.  Based on our expertise in the conduct of these studies, we are happy to consult in the design of a protocol to ensure that the protocol can be operationalized and successfully conducted.  Hereunder, we highlight key factors that are critical for successful execution of radiopharmaceutical protocols.  

• Feasibility
  • We conduct very specific and detailed site feasibility ensuring all site departments are consulted and the process flow of IMP, patients, assessments, and samples will be managed with extreme and consistent precision.
  • During feasibility and site qualification, we confirm site standard practices for infusion, injection, or inhalation and check to ensure they have appropriately calibrated equipment and mandatory processes to align with IMP administration instructions.
  • Sites often have preferred suppliers and/or process mandated equipment for administration of such radio products, and we will confirm if this is suitable for use in the study, or if different equipment will be required.  For example, we confirm that sites have specific catheters, pumps and adaptors if they are required, and conversely, we will let sites know if ancillary infusion supplies are not needed.  
  • At initial stages of site qualification and initiation, the Aixial team will ensure that all site equipment is certified and validated as this can become rate limiting.

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• Regulatory:
  • Despite the continued rise of radiopharmaceuticals in development, there is a scarcity of documented guidance for the use of radiopharmaceuticals both in the pre-clinical stage and as products enter the clinical stage[3].
  • Radiation safety issues need to be emphasized in the form of rigorous regulatory oversight to support safe and effective use, and their remains a need for harmonization of guidelines and regulations on a global scale[4].
  • Based on these aforementioned factors, it becomes critical for sponsors to have expertise ‘in-house’ through their own experts, or to obtain support from a CRO with recent and relevant experience managing global radiopharmaceuticals trials.  Considering the complexity of these trials, experienced team members are imperative.
  • Through the performance of clinical trials on a global scale, Aixial has the required regulatory submission experience and, importantly, can offer the strategic regulatory guidance required to successfully navigate the most expeditious, fast-track, approvals processes with the US FDA and EU EMEA, including both country-level and site-level radiation committees.
  • Aixial can support all required submission processes including CTA, IND, NDA, MAA and under the centralized, decentralized, mutual recognition and national European procedures.

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• Site Support
  • Provide the required training at the onset of the project; for example, in addition to routine SIV training, sites need explicit understanding regarding which samples are to be analyzed and reported locally.
  • Define a reconciliation process for central lab samples and imaging.  The communication pathway to the site management teams and sites is a critical aspect of radiopharmaceuticals trials.
  • Ensure data entry expectations e.g., real-time data entry during specific study phases, are established with sites, especially critical during dose escalation phase to evaluate the safety of each cohort.

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• Vendor Engagement:
  • Early engagement with vendors such as imaging, dosimetry, and central labs to understand study and site requirements.
  • Provide the required training at the onset of the project; for example, in addition to routine SIV training, sites need explicit understanding regarding which samples are to be analyzed and reported locally.
  • The enlistment of an established imaging vendor who have extensive site training and a user-friendly portal for scan uploads is vital aspect of these unique studies. Sites often experience unexpected uploading errors, and troubleshooting these issues with them early during the set-up phase will avoid delays downstream.  We are happy to provide the names of our qualified imaging vendors astute in the conduct of radiotherapeutic trials, if desired.
  • Providing investigators and their staff with direct contact information and 24/7 availability.

Manufacturing to meeting IP Requests 

Aixial suggests that enrollment be mapped out for all visits during the screening period to work within visit windows to enable all IP requests to be fulfilled.  Further strategy for risk mitigation include:

• Clear capacity information provided from the outset and on an ongoing basis.
  • At least 3-months’ notice of any change to manufacturing schedule (scheduled shut-downs, holiday periods, etc.).
  • Sites should be made abundantly aware of risk to treatment if visits are delayed/missed. 
  • Sites need to be trained on and understand the manufacturer’s IP Quality Control process and the importance of reviewing and filing the Certificate of Analysis.